5 research outputs found
Mecanismos moleculares de inhibiciĂłn de ATPasas transportadoras de Ca2+ / Luis Fernando Plenge Tellechea ; directores Fco. FernĂĄndez Belda, Fernando Soler Pardo.
Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. D 537.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1646
RevisioÌn: Mecanismos moleculares de la neurofibromatosis tipo 2
En este trabajo presentamos una revisioÌn sobre hallazgos maÌs relevantes de la neurofibromatosis tipo 2 (NF2), la cual se conoce por ser un desorden autosoÌmico dominante caracterizado por la presencia de schwannomas vestibulares bilaterales, aunque pueden presentarse otros tumores como meningiomas y ependimomas. Esta enfermedad es causada por diversas mutaciones en el gen NF2, mismo que codifica una proteiÌna conocida como merlina o schwannomina. Merlina estaÌ relacionada estructuralmente con la familia de proteiÌnas ERM (Ezrina-Radixina- Moesina), encargadas de acoplar las senÌales provenientes de las glucoproteiÌnas de la membrana plasmaÌtica con el citoesqueleto de actina. El gen NF2 es considerado como un supresor de tumores, y las evidencias indican que merlina funciona regulando la proliferacioÌn y el crecimiento celular. Sin embargo, los mecanismos especiÌficos por medio de los cuales merlina cumple con su funcioÌn siguen siendo un enigma. Se han identificado diversas moleÌculas que interactuÌan con merlina, lo que ha proporcionado indicios acerca de los diversos procesos celulares en los cuales esta moleÌcula participa. Entre las proteiÌnas que interactuÌan con merlina se incluyen proteiÌnas de funcioÌn estructural, receptores de membrana plasmaÌtica, proteiÌnas citosoÌlicas, GTPasas y adaptadores citoesqueleÌticos. Las mutaciones en el gen NF2 afectan la funcionalidad de merlina, lo que produce alteraciones en los mecanismos de accioÌn de merlina dando como origen a la NF2. Son necesarios maÌs estudios para determinar con certeza el papel de merlina en el control de la proliferacioÌn celular.
Abstract
In this work, we present a review over the most relevant information of the neurofibromatosis type 2 (NF2), which is known as an autosomal dominant disorder characterized by the presence of bilateral vestibular schwannomas. Other tumors such as meningiomas and ependymomas may be present. The disease is caused by mutations in the NF2 gene, which encodes a protein known as merlin or schwannomin. Merlin is structurally related to the ERM (Ezrina-Radixina-Moesina) family of proteins, a group of molecules responsible for linking the signals coming from the plasma membrane glycoproteins to the actin cytoskeleton. The NF2 gene is considered as a tumor suppressor gene, and the evidence indicates that merlin functions by regulating the cell growth and proliferation. However, the specific mechanisms through which merlin fulfill its functions as a tumor suppressor remains enigmatic. Several molecules that interact with merlin have been identified. This has provided clues to determine the cellular processes in which merlin participates. These molecules include structural proteins, plasma membrane receptors, cytosolic proteins, GTPases, and cytoskeletal adapters. Mutations in the NF2 gene affect the functionality of merlin, altering tha mecanisms of action of merlin, giving rise to NF2. Further studies are needed to determine the precise role of merlin on the control of cell proliferation.
Keywords: neurofibromatosis type 2, merlin, cytoskeleton, plasma membrane
Acanthocytosis and brain damage in area postrema and choroid plexus: Description of novel signs of Loxosceles apachea envenomation in rats.
Loxocelism is a neglected medical problem that depends on its severity, can cause a cutaneous or viscero-cutaneous syndrome. This syndrome is characterized by hemostatic effects and necrosis, and the severity of the loxoscelism depends on the amount of venom injected, the zone of inoculation, and the species. In the Chihuahuan desert, the most abundant species is L. apachea. Its venom and biological effects are understudied, including neurological effects. Thus, our aim is to explore the effect of this regional species of medical interest in the United States-Mexico border community, using rat blood and central nervous system (CNS), particularly, two brain structures involved in brain homeostasis, Area postrema (AP) and Choroid plexus (PC). L. apachea specimens were collected and venom was obtained. Different venom concentrations (0, 0.178 and 0.87 ÎŒg/g) were inoculated into Sprague-Dawley rats (intraperitoneal injection). Subsequently, blood was extracted and stained with Wright staining; coronal sections of AP were obtained and stained with Hematoxylin-Eosin (HE) staining and laminin Îł immunolabelling, the same was done with CP sections. Blood, AP and CP were observed under the microscope and abnormalities in erythrocytes and fluctuation in leukocyte types were described and quantified in blood. Capillaries were also quantified in AP and damage was described in CP. L. apachea venom produced a segmented neutrophil increment (neutrophilia), lymphocyte diminishment (leukopenia) and erythrocytes presented membrane abnormalities (acanthocytosis). Extravasated erythrocytes were observed in HE stained sections from both, AP and CP, which suggest that near to this section a hemorrhage is present; through immunohistofluorescence, a diminishment of laminin Îł was observed in AP endothelial cells and in CP ependymal cells when these structures were exposed to L. apachea venom. In conclusion, L. apachea venom produced leukopenia, netrophilia and acanthocytosis in rat peripheral blood, and also generated hemorrhages on AP and CP through degradation of laminin Îł
Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes
Abstract Background Globally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules. Currently, the effects of the overproduction of methemoglobin derived from snake venom are not extensively recorded. Therefore, the present study aims to describe the oxidative stress induced by Crotalus molossus nigrescens venom using erythrocytes. Methods Human erythrocytes were washed and incubated with different Crotalus molossus nigrescens venom concentrations (0â640Â ÎŒg/mL). After 24Â h, the hemolytic activity was measured followed by attenuated total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE, conjugated diene and thiobarbituric acid reactive substances determination. Results Low concentrations of venom (40Â ÎŒg/mL). This substance is not degraded by proteases present in the venom. By infrared spectroscopy, starting in 80Â ÎŒg/mL, we observed changes in bands that are associated with protein damage (1660 and 1540Â cmâ1) and lipid peroxidation (2960, 2920 and 1740Â cmâ1). Lipid peroxidation was confirmed by conjugated diene and thiobarbituric acid reactive substance determination, in which differences were observed between the control and erythrocytes treated with venom. Conclusions Crotalus molossus nigrescens venom provokes hemolysis and oxidative stress, which induces methemoglobin formation, loss of protein structure and lipid peroxidation